ECCEO 7 | PORTO | PORTUGAL | Daily news march 31st

HIGHLIGHTS OF THE MEETING

The morning session of Friday March 30 was related to osteoarthritis. During the first plenary lecture of the day, Professor Dere reviewed, in front of an important number of attendees, the pre-clinical and clinical data suggesting that anti-osteoprotic agents [bisphosphonates (risedronate, alendronate, zolendronate), estrogens, calcitonin and strontium ranelate] could be of potential interest for the treatment of osteoarthritis(1). However, he acknowledged that additional clinical data are needed to determine the efficacy and safety of anti-osteoporosis agents as potential new therapeutic options in the treatment of osteoarthritis.

SEARCHING FOR GENES RESPONSIBLE FOR KNEE OSTEOARTHRITIS

The first selected oral communication of the day, presented by Dr Zhai, was a study providing solid evidence for searching for genes responsible for knee osteoarthritis, particularly for progression, which has both prognostic and therapeutic potential(2). In fact, he included in his study a total of 228 monozygotic and 390 dizygotic female twins from the Twins UK registry. He showed that the heritability estimates were 47% and 49% for osteophyte and joint space narrowing, respectively and that the heritability estimates were 74% and 62% for progression of joint space narrowing and osteophyte, respectively.

The next three communications were related to the structural assessment of osteoarthritis. All these results reemphasized the clinical importance of the assessment of minimum joint space width in knee osteoarthritis but also the huge potential clinical and research interests of magnetic resonance imaging in osteoarthritis(3-5).

TREATMENT OF OSTEOARTHRITIS

The other communications of the morning session were related to the treatment of osteoarthritis. The first one evaluated, using a Markov model, the cost-effectiveness of lumiracoxib compared with celecoxib, diclofenac, ibuprofen or naproxen and the respective NSAID plus proton pump inhibitor combinations among osteoarthritis patients with a history of a gastrointestinal event and not using low-dose aspirin prophylaxis(6). Interestingly, lumiracoxib resulted in the highest quality of life adjusted life years (QALYs) in all gastrointestinal risk groups compared with all treatments. Moreover, lumiracoxib was shown to be cost-effective (defined as < £20,000/QALY gained) compared with all other treatments.

The result of the STOPP study has also been presented during this morning session(7). STOPP is a prospective, multicentre, double blind, placebo-controlled trial of chondroitin 4&6 sulfate in 622 patients with knee OA. The authors showed that chondroitin sulfate, once daily for two years, was able to significantly reduce the progression of joint space narrowing and the clinical progression in patients with knee osteoarthritis compared to placebo.

During the 6th ECCEO meeting, last year in Vienna, Professor Herrero-Beaumont presented the results of the GUIDE trial which showed the efficacy of the prescription glucosamine sulfate formulation (1500 mg once-a-day) on the symptoms of knee osteoarthritis. The aim of the study presented this year was to assess its effects on quality of life(8). Quality of life was assessed by the SF-36 questionnaire in 296 patients at randomization and repeated after 6 months. The results showed that treatment for 6 months with glucosamine sulfate improves the physical component of quality of life in knee osteoarthritis, with good correlation with its efficacy on pain and function.

SPINE OSTEOARTHRITIS PROGRESSION

In close relation with the plenary lecture, Professor Bruyere presented the results of a large study aiming to assess if a 3-year treatment with strontium ranelate can delay the progression of spinal osteoarthritis in 1105 patients with spinal osteoarthrtitis(9). He showed that strontium ranelate reduced by 42% the proportion of patients with a spine osteoarthritis progression compared to placebo. In fact, 17.1% of the patients in the placebo group experienced a spine osteoarthritis progression compared to 9.9% of the patients in the strontium ranelate group. Moreover, significantly more patients in the strontium ranelate group experienced an improvement in back pain after 3 years, compared with placebo.
For the last communication of the morning, Professor Pelletier presented a study on the therapeutic effectiveness of licofelone compared to naproxen as a disease modifying drug in 301 patients with knee OA patients using quantitative MRI and X-rays(10). This study revealed that licofelone, compared to naproxen, significantly reduces progression of knee osteoarthritis cartilage lesions (MRI assessment) but has no significant effect on X-ray progression. Both drugs were found to be equally effective at reducing OA symptoms.

This Friday March 30, two communications were also related to the effect of denosumab in patients with rheumatoid arthritis(11-12). The fist one showed that denosumab significantly reduced progression of bone erosions as assessed by magnetic resonance imaging at 6 months compared with placebo. The second one showing that denosumab reduced markers of bone and cartilage turnover in patients with rheumatoid arthritis.

The afternoon session of Friday March 30 begins with the plenary lecture of Professor Body, from Belgium, reviewing the management of osteoporosis induced by hormonal treatment of cancer (13). He reminds us that cancer treatment-induced bone loss is the most important complication of hormonal therapy for breast and prostate cancer. Indeed, it is suggested that 20 to 25% of women with treated breast cancer have low bone mineral density or osteoporotic fractures(14).

Professor Body explained to the audience that due to their improved efficacy and tolerability profiles, third-generation aromatase inhibitors are replacing tamoxifen as the preferred treatment for postmenopausal patients with both early and advanced breast cancer. However, both steroidal (exemestane) and non-steroidal aromatase inhibitors (anastrozole and letrozole) increase bone turnover, decrease bone mass and increase fracture rate. He concluded that bone mineral density should be monitored regularly in patients starting aromatase inhibitors. At least, he showed controlled studies in patients with prostate cancer demonstrating that pamidronate and zoledronic acid can prevent bone loss
under androgen deprivation therapy. However, he noted that zoledronic acid appears to be more efficient than pamidronate. He concluded by stating that a proactive rather than reactive approach to bone health is needed in patients receiving hormonal therapy for breast or prostate cancer.

IMPROVING ADHERENCE WITH OSTEOPOROSIS THERAPIES COULD HAVE AN IMPLICIT ECONOMIC VALUE IN ADDITION TO THE CLINICAL VALUE OF REDUCED FRACTURES

Other communications of the afternoon session mainly focused on persistence and compliance with anti-osteoporotic treatment(15-18). These results confirmed that adherence to current therapeutic regimens remains suboptimal and that poor compliance and non-persistence were significantly associated with greater likelihood of hip fracture and higher direct medical cost for hip fracture. Almost all studies concluded that strategies should be developed to improve both compliance and adherence in order to achieve better therapeutic outcomes in osteoporosis treatment. Improving adherence with osteoporosis therapies could have an implicit economic value in addition to the clinical value of reduced fractures. It should be pointed out that one of these communications have received the Novartis Travel Grant.

The last two oral communications of the day were related to the treatment of osteoporosis. Professor Reginster presented the first one showing that strontium ranelate 2g/day provides sustained efficacy over five years against vertebral, non-vertebral fractures compared to placebo(19). Moreover, in women at particular high risk of experiencing a hip fracture, strontium ranelate demonstrated a 43% reduction of the risk of hip fracture.

The plenary session closed with the presentation, by Professor Black and Colleagues, of the results of the HORIZON-PFT study(20). HORIZON-PFT was a multinational, 3-year, randomized, double-blind, placebo-controlled trial evaluating the potential of once-yearly zoledronic acid 5 mg, infused over 15 minutes, to decrease risk of fracture in 7736 postmenopausal osteoporotic women 65-89 years of age. Interestingly, treatment with zoledronic acid 5 mg resulted in significant relative risk reductions in morphometric vertebral fracture of 70% vs placebo and in hip fracture of 41% versus placebo. Moreover, once-yearly infusions of zoledronic acid 5 mg over 3 years were found to be safe and well tolerated. These results are complementary to the results that will be presented today, Saturday March 31, examining the effect of ZOL 5 mg on fracture rates stratified by age group (<70, 70-74, ≥75 years) and geographic region (Asia, Eastern Europe, Latin America, North America/Oceania, Western Europe) (21). The results show a significant reduction at 3 years in rates of vertebral fracture with zoledronic acid in all age groups, but there was some suggestion that the effect was greater for younger women. In addition, zoledronic acid was associated with significant reductions in vertebral and clinical fractures across geographic regions.

REFERENCES

1. Are anti-osteoporotic agents the solution for treating osteoarthritis?  W. Dere
2. Genetic contribution to knee radiographic osteoarthritis and knee alignment: a longitudinal twin study.  G. Zhai, D.J. Hart, B.S. Kato, L. Sharma, A. MacGregor, T.D. Spector
3. The loss of cartilage volume/thickness on the weight bearing areas in knee osteoarthritic patients, assessed by quantitative MRI, is correlated with severity of symptoms and worsening of pain over time.  J. Martel-Pelletier, J.P. Raynauld, M.J. Berthiaume, F. Abram, D. Choquette, B. Haraoui, J. Beary4, G. Cline, J. Meyer, J.-P. Pelletier
4. The contribution of medial femoral and tibial cartilage thickness to minimun joint space width in osteoarthritic knees. K.A. Beattie, J. Duryea, M. Pui, J. O’Neill, P. Boulos, C. Webber, F. Eckstein, J.D. Adachi
5. Minimum joint space width values in healthy individuals and patients with knee OA. K.A. Beattie, J. Duryea, M. Pui, J. O’Neill, P. Boulos, C. Webber, J.D. Adachi
6. Lumiracoxib is cost-effective compared with Celocoxib and NSAID plus proton pump inhibor combinations for the management of osteoarthritis among patients with a prior gastrointestinal event in the United Kingdom. M.  J. Huels, M. Omar, R.W. Dubois, Q.V. Doan
7. A randomized controlled trial with chondroitin sulfate involving over 600 patients: STOPP (STudy on Osteoarthritis Progression Prevention).  A. Kahan, E. Vignon, D. Uebelhart, J.-Y. Reginster
8. Glucosamine sulfate improves quality of life in patients in the Glucosamine Unum In Die Efficacy (GUIDE) trial.  G. Herrero-Beaumont, J. Branco for the GUIDE investigators
9. Strontium ranelate prevents spine osteoarthritis progression in patients with prevalent spinal osteoarthritis. O. Bruyère, D. Delferriere, C. Roux, J. Fechtenbaum, S. Kolta, J.-Y. Reginster
10. Licofelone, A 5-Lipoxygenase And Cyclooxygenase Inhibitor, Reduces The Progression Of Knee Osteoarthritis (OA): A Double Blind, Multicenter TWO-Year Study Using Quantitative MRI.  J.-P. Pelletier, J.-P. Raynauld, P. Bias, S. Laufer, B. Haraoui, D. Choquette, F. Abram, E. Vignon, J. Martel-Pelletier, and the other members of the Licofelone study group
11. Inhibition of RANKL with Denosumab decreases progression of bone erosions in patients with rheumatoid arthritis: MRI results at 6 months.  S.B. Cohen, P. Valen, C. Ritchlin, J. Schechtman, C. Peterfy, D. van der Heijde, L. Zhou, R. Newmark, W. Tsuji
12. Inhibition of RANKL with denosumab reduces markers of bone and cartilage turnover in patients with rheumatoid arthritis. N. Lane, M. Iannini, C. Atkins, B. Haraoui, L. Zhou, W. Tsuji, R. Newmark
13. Management of osteoporosis induced by hormonal treatments of cancer: clinical and economic aspects. J.J. Body
14. Bone mineral density and vertebral fracture in women with breast cancer.  E. Legrand, A. Lafitte, P. Soulié, R. Levasseur, F. Capon, E. Hoppé, D. Chappard, M. Audran
15. Adherence to therapeutic recommendation for calcium + vitamin D supplementation in the pharmacologic treatment of postmenopausal osteoporosis in Spain: the COMBICAD study. J.M. Quesada Gómez, X. Cortés, E. Ramírez
16. Impact of incomplete patient compliance with medication instructions for bisphosphonate therapy on healthcare utilization and quality of life.  J. Piercy, E. Badamgarav, E. Timpers, R. Tompkins
17. Adherence to bisphosphonates therapy and hip fracture risk in osteoporotic women. 
V. Rabenda, J.-Y. Reginster
18. Poor patient adherence to osteoporosis treatment is associated with an increased rate and cost of hip fracture.  M. Danese, E. Badamgarav, D. Bauer
19. Strontium ranelate demonstrates vertebral and non-vertebral ANTI fracture efficacy including hip fractures over 5 years in post menopausal osteoporotic women.  J.-Y. Reginster, K. Brixen, C. Cormier, J. Cannata
20. Effect of once-yearly infusion of zoledronic acid 5 mg in postmenopausal women with osteoporosis: the HORIZON Pivotal Fracture Trial.  D.M. Black, P.D. Delmas, R. Eastell, I. Reid, S. Boonen, J. Cauley, F. Cosman, P. Lakatos, P.C. Leung, Z. Man, EF. Eriksen, P. Mesenbrink, T. Hue, S. Cummings, for the HORIZON-Pivotal Fracture Trial (PFT) Research Group
21. Effect of Zoledronic Acid (ZOL) 5 mg on fracture risk by age and geographic region in women with postmenopausal osteoporosis: results from HORIZON-PFT.  J. Cauley, D. Black, S. Boonen, S. Cummings, P. Delmas, R. Eastell

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